Liver biopsy samples from 40 chronic alcoholic patients, including 9 with minimal changes of the liver, 6 with mild hepatic fibrosis, 14 with moderate fibrosis, and 11 with severe fibrosis (cirrhosis) were studied by electron microscopy to assess fibrogenesis in the Disse space and the role of fat-storing cells in this process. In the Disse space of normal liver, collagen fibers are few, and while lipid droplets containing fat-storing cells exist, their rough endoplasmic reticulum (RER) is inconspicuous. In the course of progressive hepatic fibrosis, collagen in the Disse space increased. This was significantly associated with gradual development of RER in fat-storing cells, confirmed by morphometric analysis. It is likely, therefore, that the development of RER in the fat-storing cells is a morphological correlative of their activated fibrogenesis and transformation into fibroblasts. To further clarify this, the rate of collagen synthesis was measured by the method of in vitro incorporation of [3H]proline into collagen in 17 liver biopsy samples from alcoholic patients and compared with the degree of morphological changes of RER in fat-storing cells. In liver samples with well-developed RER in fat-storing cells, a significantly higher rate of collagen synthesis was observed. These results suggest that in alcoholic liver injury, fat-storing cells may play an important role in Disse space fibrogenesis.
A histological feature of alcoholic liver disease is the presence of parenchymal fibrosis in the form of fine collagen fibers around swollen hepatocytes (1). This lesion is frequently observed in the centrilobular area and results in the formation of connective tissue septa radiating from central veins to portal tracts (2). Mallory bodies, the hallmark of alcoholic hepatitis, often coexist with parenchymal fibrosis, and a causal relation between fibrogenesis and hepatitis has been suspected (2). On the other hand, the possibility that alcohol abuse may lead to parenchymal fibrosis without the association of hepatitis or Mallory bodies has also been considered (3). Indeed, in the alcoholic baboon, which develops cirrhosis without conspicuous polymorphonuclear inflammation or Mallory bodies characteristic of human alcoholic hepatitis, Popper and Lieber have shown that a fibrotic process occurs around fatty hepatocytes with or without degenerative changes (4). In Japan, chronic liver injury from alcohol intake progresses to cirrhosis without de-